BACKGROUND: Globally, road traffic fatalities have been on the increase, particularly in low-and-middle income countries. Much of this is attributed to increases in the acquisition, and use of motorized vehicles. However, there is very little empirical research to understand the causes and determinants of this threat. This paper investigates time trends and determinants of road traffic accidents in the Kasena-Nankana district of northern Ghana. METHODS: First, we utilized causes of death data gathered by the Health and Demographic Surveillance System in Navrongo, to examine trends in deaths due to injury, particularly those related to road traffic crashes. Subsequently, we employed multivariate logistic regression to examine factors associated with deaths due to all injuries and road traffic crashes among adults 15-59 years of age. RESULTS: Results show a three-fold increase in mortality (18%) due to injuries in the Kasena-Nankana district in about a decade. Fatalities resulting from road traffic crashes constitute the greatest share of the burden of mortality resulting from injuries. Increases in road traffic fatalities have coincided with recent increases in motor and vehicular traffic in the region. Several factors are associated with the increased risk of deaths from road traffic accidents, principal among which include urban residence (OR = 1.74 95% CI 1.09-2.78), being male and in the prime adult ages of between 20-29 years old (OR = 4.85 95% CI 2.65-8.89), as well as people with higher levels of education (OR = 3.21 95% CI 1.75-5.87) and those in higher socioeconomic status categories (OR = 2.43 95% CI 1.21-4.88). CONCLUSIONS: Results suggest that road traffic fatalities have become a major cause of morbidity and mortality and brings into focus the need for measures to curb this looming crisis. There is need for strategic interventions to be adopted to avert what is sure to become one of the leading causes of death in this impoverished locality.